title: Morphine and its metabolites after patient-controlled analgesia: considerations for respiratory depression.
abstract: OBJECTIVE
  To assess concentrations of morphine and its metabolites after patient-controlled analgesia (PCA).
  
  
  METHODS
  Pilot pharmacokinetic study of morphine and pharmacokinetic simulation.
  
  
  METHODS
  Post-anesthesia care room and ward of an academic teaching hospital.
  
  
  METHODS
  10 ASA physical status I, II, and III postoperative surgical patients.
  
  
  METHODS
  Patients received morphine via PCA by routine hospital protocols.
  
  
  METHODS
  The population mean plasma and effect-site concentrations of morphine, morphine-6-glucuronide (M6G), and morphine-3-glucuronide (M3G) was simulated in 4 patient group scenarios: morphine PCA used alone, morphine PCA used with continuous background morphine infusion of 0.5 mg/hr, morphine PCA used with continuous background morphine infusion of 1.0 mg/hr, and morphine PCA used with continuous background morphine infusion of 2.0 mg/hr.
  
  
  RESULTS
  The 4 groups exhibited simulated peak morphine, M6G, and M3G effect-site concentrations at 8 to 24 hours post-infusion. The highest peak morphine, M6G, and M3G effect-site concentrations decreased in the following order by group: 2.0 mg/hr morphine infusion + PCA group, 1.0 mg/hr morphine infusion + PCA group, and 0.5. mg/hr morphine infusion + PCA group.
  
  
  CONCLUSIONS
  Patients receiving morphine PCA should be monitored closely from 8 to 24 hours postoperatively. Morphine PCA given with background infusion rates up to 1.0 mg/hr does not offer distinct pharmacokinetic advantages over morphine PCA alone. Morphine PCA with background infusion rate of 2.0 mg/hr is associated with the greatest risk of respiratory depression.
authors.affiliation: Department of Anesthesia, Stanford University, H3580, 300 Pasteur Dr, Stanford, CA 94305-5640, USA.
authors.forename: Wai Johnn
authors.initials: WJ
authors.lastname: Sam
authors.forename: Sean C
authors.initials: SC
authors.lastname: MacKey
authors.forename: Jörn
authors.initials: J
authors.lastname: Lötsch
authors.forename: David R
authors.initials: DR
authors.lastname: Drover
mesh_terms: D016058:Analgesia, Patient-Controlled / Q000009:adverse effects / Q000379:methods*; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007262:Infusions, Intravenous; D009020:Morphine / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D010149:Postoperative Pain / Q000188:drug therapy; D010865:Pilot Projects; D011446:Prospective Studies; D012131:Respiratory Insufficiency / Q000209:etiology*; D013997:Time Factors
chemical_list: D000701:Analgesics, Opioid; D009020:Morphine